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Small cell lung cancer

B cell lymphoma 2
(BCL-2; BCL2); Bcl-XL

Cell culture and mouse studies identified inhibitors of BCL-2 and Bcl-XL that could help treat small cell lung cancer. In human small cell lung cancer lines, 4,5-diphenyl-1H-pyrrole-3-carboxylic acid-based BCL-2 and Bcl-XL inhibitors designed using structure-based optimization induced cell death more potently than clinical-stage inhibitors, including ABT-263. In mouse xenograft models of human small cell lung cancer, the most potent inhibitor induced apoptosis and tumor regression that prevented tumor growth for at least 15 days. Next steps could include testing the inhibitors in additional animal models of small cell lung cancer.
Abbott Laboratories and Roche's Genentech Inc. unit have the BCL-2-family protein inhibitor ABT-263 in Phase I/II testing to treat small cell lung cancer.
At least seven other companies have inhibitors of BCL-2-family proteins in clinical and preclinical testing to treat cancers.

SciBX 5(41); doi:10.1038/scibx.2012.1082
Published online Oct. 18, 2012

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Chen, J. et al. J. Med. Chem.; published online Oct. 2, 2012;
Contact: Shaomeng Wang, University of Michigan, Ann Arbor, Mich.